American Journal of Pharmacogenomics: Genomics-Related Research in Drug Development and Clinical Practice
No specific gene has been identified for any major psychiatric disorder, including schizophrenia, in spite of strong evidence supporting a genetic basis for these complex and devastating disorders. There are several likely reasons for this failure, ranging from poor study design with low statistical power to genetic mechanisms such as polygenic inheritance, epigenetic interactions, and pleiotropy. Most study designs currently in use are inadequate to uncover these mechanisms.
Revista De Investigacion Clinica; Organo Del Hospital De Enfermedades De La Nutricion
The dopamine D4 receptor (DRD4) is the most important gene in psychiatric genetics since its involvement in the physiology of behavior, pharmacology response and psychopathology. DRD4's sequence gene present some polymorphism such as in the exon 3 constituted from 2 to 10 copies of repetitive sequences of 48 base pair (bp), from class variable number tandem repeats (VNTR). An additional genetic variant in the exon 1 presents polymorphisms to 12 bp VNTR, and the variation -521 C by T of the promoter region.
Glutamatergic signaling is regulated, in part, through differential expression of NMDA and AMPA/KA channel subunits and G protein-coupled metabotropic receptors. In human brain, region-specific expression patterns of glutamate receptor genes are maintained over the course of decades, suggesting a role for molecular mechanisms involved in long-term regulation of transcription, including methylation of lysine residues at histone N-terminal tails.
Genetic studies implicating the region of human chromosome 18p11.2 in susceptibility to bipolar disorder and schizophrenia have observed parent-of-origin effects that may be explained by genomic imprinting. We have identified a transcriptional variant of the GNAL gene in this region, employing an alternative first exon that is 5' to the originally identified start site. This alternative GNAL transcript encodes a longer functional variant of the stimulatory G-protein alpha subunit, Golf.
BACKGROUND: Schizophrenia is frequently accompanied by hypometabolism and altered gene expression in the prefrontal cortex. Cellular metabolism regulates chromatin structure, including covalent histone modifications, which are epigenetic regulators of gene expression. OBJECTIVE: To test the hypothesis that down-regulated metabolic gene expression is associated with histone modification changes in the prefrontal cortex of subjects with schizophrenia.
In mammals the neonatal period is a time of significant social interaction. This is true even in solitary species as females spend a significant amount of time nursing and caring for their offspring. In social species interactions may also include the father, older siblings and extended family members. This period is a time of significant development, including organization of the central nervous system, and therefore a time when the degree and type of social interaction influences the development and expression of social behavior in adulthood.
Molecular data and gene expression data and recently mitochondrial genes and possible epigenetic regulation by non-coding genes is revolutionizing our views on schizophrenia. Genes and epigenetic mechanisms are triggered by cell-cell interaction and by external stimuli. A number of recent clinical and molecular observations indicate that epigenetic factors may be operational in the origin of the illness.
Journal of Neural Transmission (Vienna, Austria: 1996)
DNA methyltransferases (DNMTs) are involved within the epigenetic control of DNA methylation processes. Recently, it has been shown that the genomic DNA methylation in patients with alcoholism is increased. In the present controlled study we observed a significant decrease of mRNA expression of DNMT-3a and DNMT-3b when comparing alcoholic patients (n = 59) with healthy controls (n = 66): DNMT-3a (t = -2.38, p = 0.019), DNMT-3b (t = -2.65, p = 0.008). No significant differences were seen for DNMT-1 and Mbd-2 (Methyl-CpG-Binding-Domain protein 2) expression.
Journal of Child Psychology and Psychiatry, and Allied Disciplines
Gene-environment interplay is a general term that covers several divergent concepts with different meanings and different implications. In this review, we evaluate research evidence on four varieties of gene-environment interplay. First, we consider epigenetic mechanisms by which environmental influences alter the effects of genes. Second, we focus on variations in heritability according to environmental circumstances. Third, we discuss what is known about gene-environment correlations.